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Clinical, laboratory and outcome data were reviewed for pediatric patients who were diagnosed with chronic myeloid leukemia (CML) and managed at two tertiary care hospitals in Saudi Arabia, between January 2011 and December 2017 to assess the response to tyrosine kinase inhibitors (TKI) focusing on the monitoring of BCR-ABL fusion gene transcript levels and to look at the overall outcome.CML patients were identified based on the cytogenetic and molecular results.Twelve pediatric patients diagnosed with CML at a median age of 8.4 year; treated with TKI as first-line therapy, 11 (91.7%) patients were started with imatinib (first-generation TKI), while one received dasatinib (second-generation TKI) due to his three-way Philadelphia chromosome sensitivity. Eight patients (72.7%) starting on imatinib were switched to dasatinib (six patients due to drug resistance, and two patients due to intolerance of Imatinib) and two patients (25%) of whom had already achieved major molecular response (MMR) on Imatinib. Response rate to imatinib in terms of achieving MMR as first-line therapy was achieved in five out of 11 patients (45.5%) and only three of them continued to maintain their MMR. Six out of eight patients who were switched to dasatinib achieved MMR. Two patients underwent hematopoietic stem cell transplant (SCT): one due to blast crisis and one due to the side effects of TKI. With a median follow-up time of 78 months (range, 40.5-108), all of our patients were alive at last update.We report an excellent outcome with an overall survival (OS) of 100% at 5-year and disease-free survival (DFS) of 91.7% (8.0%). All our patients achieved MMR and only one patient had loss of MMR on follow-up. Eight patients (66.7%) achieved complete molecular response (CMR).

Stem cell transplantation (HCT) restores normal hematopoiesis in Fanconi anemia patients but survivors remain prone to long-term complications. This study was conducted to review the late effects and psychosocial adjustment in life for long term survivors of FA patients. Medical records of 149 patients with FA who underwent allogeneic HCT were reviewed. Cumulative probabilities of OS at 10- and 15 years were 76.6%±3.6% and 69.8%±4.4% respectively. Median OS time was 22.8 years. Eighty-seven patients were successfully contacted for follow up. Late-effects were reported by 47. The most commonly reported late-effects were hypothyroidism, amenorrhea and ocular problems. About two-third of our alive patients (n = 58, 66.7%) had achieved a minimum of high school education; only three (3.4%) got married. None had children. Of those 45 patients who were above 20 years of age at last contact, 42 (93.3%) were still living with their parents, two (5.0%) had rental accommodation and one female was living independently. Only nine (20%) of recipients who were above 20 years of age were able to secure an employment, two of whom were self-employed. Long term close follow-up is crucial to detect such complications. Psychological and social counseling should be an integral part of their follow up.

Table S1: Data set country allocation; Table S2. A Cox regression model for 2 year overall survival considering top predictors- no interactions considered; Table S3. A Cox regression model for 2 year overall survival considering top predictors with interactions considered; Table S4: Population characteristics of a randomly selected imputed data set; Table S5. Risk for 2-years OS and 2-years LFS categorized by the UCBT score; Table S6. Probabilities for OS, LFS, NRM, and RI stratified by the UCBT score over 20 imputed datasets; Table S7: The population characteristics across the UCBT risk score categories over the validation set; Figure S1. Estimation of predictor importance using the Random Survival Forest minimal depth; Figure S2: Interaction analysis using conditional plots; Figure S3: A calibration plot of the risk scores between predicted and observed events (death) at two years, according to pentiles.

Purpose: Survival of acute leukemia (AL) patients following umbilical cord blood transplantation (UCBT) is dependent on an array of individual features. Integrative models for risk assessment are lacking. We sought to develop a scoring system for prediction of overall survival (OS) and leukemia-free survival (LFS) at 2 years following UCBT in AL patients.Experimental Design: The study cohort included 3,140 pediatric and adult AL UCBT patients from the European Society of Blood and Marrow Transplantation and Eurocord registries. Patients received single or double cord blood units. The dataset was geographically split into a derivation (n = 2,362, 65%) and validation set (n = 778, 35%). Top predictors of OS were identified using the Random Survival Forest algorithm and introduced into a Cox regression model, which served for the construction of the UCBT risk score.Results: The score includes nine variables: disease status, diagnosis, cell dose, age, center experience, cytomegalovirus serostatus, degree of HLA mismatch, previous autograft, and anti-thymocyte globulin administration. Over the validation set an increasing score was associated with decreasing probabilities for 2 years OS and LFS, ranging from 70.21% [68.89–70.71, 95% confidence interval (CI)] and 64.76% (64.33–65.86, 95% CI) to 14.78% (10.91–17.41) and 18.11% (14.40–22.30), respectively. It stratified patients into six distinct risk groups. The score's discrimination (AUC) over multiple imputations of the validation set was 68.76 (68.19–69.04, range) and 65.78 (65.20–66.28) for 2 years OS and LFS, respectively.Conclusions: The UCBT score is a simple tool for risk stratification of AL patients undergoing UCBT. Widespread application of the score will require further independent validation. Clin Cancer Res; 23(21); 6478–86. ©2017 AACR.

Saudi Arabia is the largest of the Arabian Gulf countries with a total population of 33.41 million as of 2017. This report summarizes the experience from four leading tertiary care hematopoietic stem cell transplantation (HSCT) centers in Saudi Arabia representing more than 90% of all HSCTs performed in the country. Between 1984 and 2016, a total of 6,184 HSCTs were performed. Of these, 3,586 HSCTs were performed in adults and 2,598 HSCTs were performed in pediatric patients. Malignancy was the main indication for transplantation (47%). While most transplants were performed from an identical sibling donor, HSCTs from cord blood, unrelated and, more recently, haploidentical donors have also been performed. Relative shortage of HSCT bed capacity is perceived to be a limiting factor in Saudi Arabia. Lately, more HSCT centers are emerging with rapid growth, which may significantly improve the access to HSCT in the country in the near future.

Background and Objective Neuroblastoma is the most common extracranial solid tumor found in pediatric patients. High-risk neuroblastoma (HR-NBL) can be characterized by metastasis, age, and other tumor characteristics that result in an adverse outlook for this patient cohort. The standard of care includes induction chemotherapy, surgery, followed by stem cell autologous transplant (ASCT), and later, antidisialoganglioside (anti-GD2) antibodies. In this study, we provide the survival and toxicity data of our HR-NBL patients treated with a single ASCT. Methods We retrospectively analyzed pediatric HR-NBL patients treated with single ASCT after a carboplatin, etoposide, and melphalan (CEM) regimen in our institution between January 1993 and December 2014. Results There were 99 evaluable patients with male predominance. The median age at diagnosis was 3 years. Most of our HR-NBL patients were stage 4 (88%). All patients received ASCT. Peripheral blood was the graft source in 58% of the patients. Time for hematological count recovery with bone marrow as a graft source was prolonged but not statistically significant when compared with PBSCs. Of all the patients, 58% received radiation therapy to residual disease. Overt secondary leukemia was not seen in any of these patients. Three-year overall survival (OS) was 68.5% ± 5.2% and the 3-year event-free survival (EFS) was (48.3% ± 5.2%). Conclusion Our HR-NBL patients tolerated high-dose chemotherapy well followed by single autologous stem cell transplant. Tandem transplant is a feasible option in our patient cohort. Apart from secondary solid tumors, there were no long-term complications seen.

Aims This prospective interventional study aimed to assess the efficacy of supersaturated calcium phosphate rinse and the use of an extra‐soft toothbrush twice a day when added to the existing oral hygiene protocol regimen (0.12% chlorhexidine gluconate + 3% sodium bicarbonate + nystatin 5000 U/mL) in reducing the severity of oral mucositis among pediatric patients receiving chemotherapy for the hematopoietic stem cell transplant. Methods Forty‐five patients that received chemotherapy for the hematopoietic stem cell transplant were randomly allocated to three groups of 15 patients each. Group A was advised to follow the existing oral hygiene protocol regimen (Control), group B was advised to brush their teeth twice daily using an extra‐soft toothbrush and to follow the control regimen, and lastly group C was advised to use supersaturated calcium phosphate rinse and to follow the control regimen. Oral mucositis was recorded according to World Health Organization criteria from the day of admission (day 1) to the day of discharge (day 28). The incidence of oral mucositis between the three groups was compared using the Kruskall‐Wallis test while the severity of oral mucositis between the three groups was compared using a one‐way ANOVA test. Results The results of the study showed no significant difference in the incidence of oral mucositis between the three groups; however, there was a lower severity of oral mucositis in the supersaturated calcium phosphate rinse group when compared to the control group or the group who used an extra‐soft toothbrush with the control regimen. Conclusion Although marginally fewer cases and lower severity of oral mucositis was observed in the group using supersaturated calcium phosphate rinse, the lack of statistical significance suggests that the evidence for their use is not conclusive. The results of this study also showed that the introduction of an extra‐soft toothbrush into the oral hygiene regimen did not significantly reduce the incidence of oral mucositis and may actually be responsible for an increase in the severity of oral mucositis.

In 2010, we reported the outcome of hematopoietic stem cell transplantation (HSCT) in 11 children with Griscelli syndrome type 2 (GS2). We report here the update on this cohort to include 35 patients. Twenty-seven (77%) patients received conditioning regimen including busulfan, cyclophosphamide with etoposide. Eight (23%) were given busulfan, fludarabine. Thiotepa was added to busulfan and fludarabine regimen in two patients; one received haploidentical marrow and one unrelated cord blood. Posttransplant clinical events included veno-occlusive disease (n = 7), acute (n = 8), or chronic (n = 1) graft-versus-host disease II–IV. With a mortality rate of 37.1% (n = 13) and a median follow-up of 87.7 months of the survivors, 5-year cumulative probability of overall survival (OS) for our cohort of patients was 62.7% (±8.2%). Cumulative probability of 5-year OS was significantly better in those who did not have hemophagocytic lymphohistiocytosis (HLH) prior to HSCT (100% vs. 53.3 ± 9.5%, P value: 0.042). Of the 16 patients with neurologic involvement before HSCT, 8 survived and 3 presented sequelae. OS at 5-year was 50 ± 12.5% and 73.3 ± 10.2% (P value: 0.320) in patients with and without CNS involvement, respectively. In conclusion, HSCT in patients with GS2 is potentially curative with long-term disease-free survival. Early HSCT before the development of the accelerated phase is associated with a better outcome.

Background : Graft failure (GF) is a life-threatening complication after allogeneic hematopoietic stem cell transplantation (HCT). In the absence of autologous recovery, a second HCT is necessary to attempt preventing death due to prolonged pancytopenia. Previous studies describing outcomes of second HCT performed after a GF with different types of donor sources report a wide range of overall survival (OS) and transplant related mortality (TRM), however studies including a large number of patients receiving a second transplant with umbilical cord blood as the graft source are scarce. Objective : To describe umbilical cord blood transplants (UCBT) performed after GF following a previous HCT. Study Design : Retrospective registry-based study, using data extracted from Eurocord and the European Society for Blood and Marrow Transplantation (EBMT) databases. The study reports outcomes of 247 umbilical cord blood transplants (UCBT), performed in EBMT transplant centers, after GF following a previous HCT. Data were analyzed separately for patients with malignant (n=141) and non-malignant diseases (n=106). Results : The most frequent HCT that resulted in GF was also UCBT (65.0% and 68.9%), and most GF occurred within 100 days after transplantation (92.3% and 85.9%), for malignant and non-malignant diseases, correspondingly. Median follow-up was 47 for surviving patients with malignant and 38 months for those with non-malignant diseases. We observed a similar cumulative incidence of neutrophil engraftment of 59.1% (95% CI 51.4- 67.9%) and 60.4% (95% CI 51.7- 70.6%), in a median time of 23 and 24 days for malignant and non-malignant diseases, respectively. The 3-year OS was 28.9% (95% CI 21.8- 37.3%) in the malignant disease group and 49.1% (95% CI 39.5- 58.8%) in the non-malignant. In patients with malignancies, TRM was 39.9% (95%CI 32.5 - 49.1%) at 100 days and malignant 57.5% (95%CI 49.4 - 66.8%) at 3 years. In multivariate analyses, none of the characteristics studied were statistically significantly associated with engraftment or overall survival. Conclusion : Although survival for patients requiring a second transplant is not optimal, UCB remains a valid life-saving option for patients with GF.

Congenital sideroblastic anaemias (CSA) are a rare group of disorders characterized by the presence of pathologic iron deposits within the mitochondria of erythroid precursors (ring sideroblasts) in the bone marrow due to heterogenous germline mutations leading to defects in mitochondrial heme synthesis, iron-sulfur (Fe-S) cluster biogenesis, or protein synthesis. Patients present with anaemia and relative reticulocytopenia, and systemic iron overload secondary to chronic ineffective erythropoiesis, leading to end-organ damage. The disease is heterogenous underlying the genetic variability and the variable response to treatment. Although a number of CSA patients have received a bone marrow transplant, the outcomes and toxicities are not known. This status makes it very difficult to understand the role of BMT in the management of CSA. A search in the EBMT database identified 28 patients receiving a HSCT for CSA between 1998 to 2018 by 24 participating centres. The median year of transplantation was 2014 (IQR 2004-2016). The distribution was equal between males (n=14) and females (n=14). The median age at transplantation was 7 years of age (3-10 years). Fifteen patients had a sibling HSCT (88%), one a family matched donor HSCT (6%) and one an unrelated matched (6%), the type of transplant being unknown in others (n=11). The source of stem cells was bone marrow in 20 cases (74%), peripheral blood in 4 cases (15%), cord blood in 2 (7%) and combined bone marrow and cord in one (4%). Five cases had a Bu/Cy based conditioning regimen, 4 had Bu/fludarabine based regimen and three fludarabine/treosulfan based conditioning with the rest having a variety of approaches. Eighty-six percent of cases had serotherapy with ATG or alemtuzumab. The median follow-up was 31.6 months (95% CI, 12.2-74.1%). The overall survival at 12 and 24 months was 88% (76-100) and 82% (66-99), respectively (figure 1). The median neutrophil engraftment was 18 (15-21) days and platelet engraftment >20 x 109/L was 29 (20-51) days, with a graft failure incidence of 7% (0-17) at 12 months. Two patients suffered from VOD. There were four deaths, three of which were related to transplant complications. The event free survival (survival without graft failure, relapse and second transplant) at 12 and 24 months was 85% (72-99) (figure 2). Six patients developed acute GvHD grade II and one case grade III; giving a grade II/III incidence of 28% (10-46). There was one case of limited and one of chronic GvHD, giving an incidence of 11% (0-26%) at 12 months and 24 months. In conclusion, whilst HSCT for CSA is a rare occurrence, these data demonstrate that HSCT for this condition is feasible and the outcomes are in keeping with those obtained for transplantation for transfusion dependent anaemias during the same time-period. Disclosures Handgretinger: Amgen: Honoraria. Moraleda:Gilead: Consultancy, Other: Travel Expenses; Jazz Pharmaceuticals: Consultancy, Research Funding; Novartis: Consultancy, Other: Travel Expenses; Sandoz: Consultancy, Other: Travel Expenses; Takeda: Consultancy, Other: Travel Expenses. Risitano:Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Alnylam: Research Funding; Alexion: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Jazz: Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees; Samsung: Membership on an entity's Board of Directors or advisory committees; Amyndas: Consultancy; RA pharma: Research Funding; Biocryst: Membership on an entity's Board of Directors or advisory committees; Apellis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Achillion: Membership on an entity's Board of Directors or advisory committees; Pfizer: Speakers Bureau. Peffault De Latour:Amgen: Research Funding; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Apellis: Membership on an entity's Board of Directors or advisory committees; Alexion Pharmaceuticals Inc.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.

In MDS, the bone marrow produces abnormal, immature blood cells called blast cells. Imprecise, in half of pediatric MDS, blast count is normal. A retrospective observational study was conducted to review the outcome of our HCT in pediatric patients with MDS. Record of 35 MDS patients after BMT, 1993-2016, were reviewed. Median age at transplant was 4 yrs (0.8-14.8) and median time to transplant from diagnosis 8.1 (2.3-102.5) months. TRM was 17.1% (6); [low risk (LR) = 5 (19.2%) and high risk (HR) = 1 (11.1%)] MDS group succumbed within first 100 days. The rest were fully engrafted; [low risk = 21 (72.4%) and high risk = 8 (27.6%)]. Primary and secondary graft failure was observed in one patient each (2.9%). VOD was seen in 2 patients (5.7%) and 5 (14.3%) had hemorrhagic cystitis. With a median follow-up of 112.4 months and 12 events of mortality, 3-years OS was 68.1% ± 8.0%. No significant risk factor including age, time to transplant, disease risk group, gender, conditioning regimen, source of stem cells, or a GvHD through uni- or multi-variable analyses were found to be associated with OS. Bu/Cy/±ATG conditioning regimen showed a trend of superiority for OS and EFS in our small series. The relapse incidence in our cohort was 11.5% in LR MDS.

HLA-haploidentical transplantation (haplo-HCT) using post-transplantation-cyclophosphamide (PT-Cy) is a feasible procedure in children with malignancies. However, large studies on Haplo-HCT with PT-Cy for childhood acute lymphoblastic leukemia (ALL) are lacking. We analyzed haplo-HCT outcomes in 180 children with ALL. Median age was 9 years, and median follow-up was 2.7 years. Disease status was CR1 for 24%, CR2 for 45%, CR+3 for 12%, and active disease for 19%. All patients received PT-Cy day +3 and +4. Bone marrow (BM) was the stem cell source in 115 patients (64%). Cumulative incidence of 42-day engraftment was 88.9%. Cumulative incidence of day-100 acute graft-versus-host disease (GVHD) grade II-IV was 28%, and 2-year chronic GVHD was 21.9%. At 2 years, cumulative incidence of nonrelapse mortality (NRM) was 19.6%. Cumulative incidence was 41.9% for relapse and 25% for patients in CR1. Estimated 2-year leukemia free survival was 65%, 44%, and 18.8% for patients transplanted in CR1, CR2, CR3+ and 3% at 1 year for active disease. In multivariable analysis for patients in CR1 and CR2, disease status (CR2 [hazard ratio {HR} = 2.19; P = .04]), age at HCT older than 13 (HR = 2.07; P = .03) and use of peripheral blood stem cell (PBSC) (HR = 1.98; P = .04) were independent factors associated with decreased overall survival. Use of PBSC was also associated with higher NRM (HR = 3.13; P = .04). Haplo-HCT with PT-Cy is an option for children with ALL, namely those transplanted in CR1 and CR2. Age and disease status remain the most important factors for outcomes. BM cells as a graft source is associated with improved survival.

Chronic granulomatous disease (CGD) is a primary immunodeficiency resulting in life-threatening infections and inflammatory complications. Allogeneic hematopoietic cell transplantation (allo-HCT) can cure the disease, but the indication to transplant remains controversial. We performed a retrospective multicenter study of 712 patients with CGD who underwent allo-HCT transplantation from March 1993 through December 2018. We studied 635 children (aged 1 antigen mismatch. Choice of conditioning regimen did not influence OS or EFS. In summary, we report an excellent outcome after allo-HCT in CGD, with low incidence of graft failure and mortality in all ages. Older patients and recipients of 1-antigen-mismatched grafts had a less favorable outcome. Transplantation should be strongly considered at a younger age and particularly in the presence of a well-matched donor.